Host response to vaccination has historically been evaluated based on a change in antibody titer that compares the post-vaccination titer to the pre-vaccination titer. A four-fold or greater increase in antigen-specific antibody has been interpreted to indicate an increase in antibody production in response to vaccination. New technologies, such as the bead-based assays, provide investigators and clinicians with precise antibody levels (reported as concentration per mL) in ranges below and above those previously available through standard assays such as ELISA. Evaluations of bead assay data to determine host response to vaccination using fold change and absolute change, witha general linear models used to calculate adjusted statistics, present very different pictures of the antibody response when pre-vaccination antibody levels are low. Absolute changes in bead assay values, although not a standard computation, appears to more accurately reflect the host response to vaccination for those individuals with extremely low pre-vaccination antibody levels. Conversely, for these same individuals, fold change may be very high while post-vaccination antibodies do not achieve seroprotective levels. Absolute change provides an alternate method to characterize host response to vaccination, especially when pre-vaccination levels are very low, and may be useful in studies designed to determine associations between host genotypes and response to vaccination.

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We present a new approach for aligning families of 2D gels. Instead of choosing one of the gels as reference and performing a pairwise alignment, we construct an ideal gel that is representative of the entire family and obtain a set of piecewise affine transformations that optimally align each gel of the family to the ideal gel. The coefficients defining the transformations as well as the ideal landmarks are obtained as the solution of a large-scale quadratic programming problem that can be solved efficiently by interior-point methods.

Differences in immunological response among vaccine recipients are determined both by their genetic differences and environmental factors. Knowledge of genetic determinants of immunological response to a vaccine can be used to design a vaccine that circumvents immunogenetic restrictions. The currently available vaccine for typhoid is a pure polysaccharide vaccine, immune response to which is T-cell independent. Little is known about whether genetic variation among vaccinees associates with variation in their antibody response to a polysaccharide vaccine. We conducted a study on 1,000 individuals resident in an area at high-risk for typhoid; vaccinated them with the typhoid vaccine, measured their antibody response to the vaccine, assayed [2,000 curated SNPs chosen from 283 genes that are known to participate in immune-response; and analyzed these data using a strategy to (a) minimize the statistical problems associated with testing of multiple hypotheses, and (b) internally cross-validate inferences, using a half-sample design, with little loss of statistical power. The first stage analysis, using the first half-sample, identified 54 SNPs in 43 genes to be significantly associated with immune response. In the second-stage, these inferences were cross-validated using the second half-sample. First-stage results of only 8 SNPs (out of 54) in 7 genes (out of 43) were cross-validated. We tested additional SNPs in these 7 genes, and found 8 more SNPs to be significantly associated. Haplotypes constructed with these SNPs in these 7 genes also showed significant association. These 7 genes are DEFB1, TLR1, IL1RL1, CTLA4, MAPK8, CD86 and IL17D. The overall picture that has emerged from this study is that (a) immune response to polysaccharide antigens is qualitatively different from that to protein antigens, and (b) polymorphisms in genes involved in polysaccharide recognition, signal transduction, inhibition of T-cell proliferation, pro-inflammatory signaling and eventual production of antimicrobial peptides are associated with antibody response to the polysaccharide vaccine for typhoid.

Vi polysaccharide from Salmonella enterica serotype Typhi is used as one of the available vaccines to prevent typhoid fever. Measurement of Vi-specific serum antibodies after vaccination with Vi polysaccharide by enzyme-linked immunosorbent assay (ELISA) may be complicated due to poor binding of the Vi polysaccharide to ELISA plates resulting in poor reproducibility of measured antibody responses. We chemically conjugated Vi polysaccharide to fluorescent beads and performed studies to determine if a bead-based immunoassay provided a reproducible method to measure vaccine-induced anti-Vi serum IgG antibodies. Compared to ELISA, the Vi bead immunoassay had a lower background and therefore a greater signal-to-noise ratio. The Vi bead immunoassay was used to evaluate serum anti-Vi IgG in 996 subjects from the city of Kolkata, India, before and after vaccination. Due to the location being one where Salmonella serotype Typhi is endemic, approximately 45% of the subjects had protective levels of anti-Vi serum IgG (i.e., 1 g/ml anti-Vi IgG) before vaccination, and nearly 98% of the subjects had protective levels of anti-Vi serum IgG after vaccination. Our results demonstrate that a bead-based immunoassay provides an effective, reproducible method to measure serum anti-Vi IgG responses before and after vaccination with the Vi polysaccharide vaccine.